定期提供乙醇作为实现秀丽隐杆线虫幼虫无限寿命的途径。

IF 3.3 Q2 GERIATRICS & GERONTOLOGY
Frontiers in aging Pub Date : 2023-09-05 eCollection Date: 2023-01-01 DOI:10.3389/fragi.2023.1031161
Xingyu Zhang, Sider Penkov, Teymuras V Kurzchalia, Vasily Zaburdaev
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引用次数: 0

摘要

dauer幼虫是蠕虫发育的一个特殊阶段,为在恶劣条件下生存而优化,已被用作抗应激、代谢适应和寿命的模型。最近的研究结果表明,秀丽隐杆线虫的dauer幼虫可能利用外部乙醇作为能源来延长其寿命。研究表明,虽然乙醇可能是一种有效的无限能量来源,但一些有毒化合物作为其代谢的副产物积累可能会导致线粒体损伤,从而限制幼虫的寿命。提出了一个极小数学模型来解释dauer幼虫的寿命与其乙醇代谢之间的联系。为了从理论上探索是否有可能进一步延长dauer幼虫的寿命,我们引入了两种自然机制,描述了受损线粒体的恢复和有毒化合物的消除,这两种机制以前在模型中被省略了。对修正模型的数值模拟表明,虽然乙醇浓度不变,但寿命仍然有限。然而,如果以适当的频率和幅度定期供应乙醇,只要我们观察到系统,dauer就可以存活。分析方法进一步有助于解释喂食频率和幅度如何影响寿命延长。在将模型与固定乙醇浓度的实验数据进行比较的基础上,我们提出了可以延长dauer存活时间的喂养方案范围,并可以进行实验测试。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Periodic ethanol supply as a path toward unlimited lifespan of <i>Caenorhabditis elegans</i> dauer larvae.

Periodic ethanol supply as a path toward unlimited lifespan of <i>Caenorhabditis elegans</i> dauer larvae.

Periodic ethanol supply as a path toward unlimited lifespan of <i>Caenorhabditis elegans</i> dauer larvae.

Periodic ethanol supply as a path toward unlimited lifespan of Caenorhabditis elegans dauer larvae.

The dauer larva is a specialized stage of worm development optimized for survival under harsh conditions that have been used as a model for stress resistance, metabolic adaptations, and longevity. Recent findings suggest that the dauer larva of Caenorhabditis elegans may utilize external ethanol as an energy source to extend their lifespan. It was shown that while ethanol may serve as an effectively infinite source of energy, some toxic compounds accumulating as byproducts of its metabolism may lead to the damage of mitochondria and thus limit the lifespan of larvae. A minimal mathematical model was proposed to explain the connection between the lifespan of a dauer larva and its ethanol metabolism. To explore theoretically if it is possible to extend even further the lifespan of dauer larvae, we incorporated two natural mechanisms describing the recovery of damaged mitochondria and elimination of toxic compounds, which were previously omitted in the model. Numerical simulations of the revised model suggested that while the ethanol concentration is constant, the lifespan still stays limited. However, if ethanol is supplied periodically, with a suitable frequency and amplitude, the dauer could survive as long as we observe the system. Analytical methods further help to explain how feeding frequency and amplitude affect lifespan extension. Based on the comparison of the model with experimental data for fixed ethanol concentration, we proposed the range of feeding protocols that could lead to even longer dauer survival and it can be tested experimentally.

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